Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

The mechanisms underpinning concussion, traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE) are poorly understood. Using neuropathological analyses of brains from teenage athletes, a new mouse model of concussive impact injury, and computational simulations, Tagge et al. show that head injuries can induce TBI and early CTE pathologies independent of concussion.

Three patients with mosaicism and a cell line containing a small ring (X) chromosome are described. Their phenotype is similar to several previously reported patients with a 45,X/46,X,r(X) karyotype and a phenotype far more severely affected than expected in Turner's syndrome. The clinical picture includes mental retardation, a facial appearance reminiscent of the Kabuki make up syndrome, and limb anomalies. Some of the patients also had streaky hyperpigmentation of the skin in a pattern suggesting dermal mosaicism. It (fig 1).The baby subsequently suffered from recurrent wheezing and chest infections. Her developmental and growth delay persisted. At the age of 33 months her length was 3-4 SD and her weight 2-3 SD below the mean for her age. She died at the age of 35 months.The cytogenetic results have been reported in full by Jacobs et al.1 Briefly the majority of the patient's blood leucocytes had a 45,X constitution, the X being inherited from the father. However, 15 of 200 cells had a ring (X) smaller than a G group chromosome while nine cells had two ring chromosomes, one smaller than a G group and one minute. In situ hybridisation with the X centromere probe pSV2X5 confirmed that both ring chromosomes were derived from X chromosome material, presumably that of the mother. Studies of the replication status of the two ring chromosomes were attempted using a terminal pulse of BrdU, but both rings were found to be too small to give accurate results. CASE 2Case 2 (89-1479) was the second child of a healthy 32 year old mother and 33 year old father. The pregnancy was complicated by polyhydramnios and she was born after spontaneous labour at 37 weeks' gestation, weighing 2950 g. Limb abnormalities were noted at birth. She had a short right arm and the right hand had a thumb and two fingers only, all digits being broad and short. The left arm and hand were normal in size but all the digits were broad and short. The right leg and foot were normal but the left femur was slightly short and the left fibula was absent. There was syndactyly of the lateral three toes. The unequal leg length necessitated a below knee amputation at 8 years.As a baby she fed badly owing to palatal incoordination and had slow weight gain.

Paternal duplications of distal 11p result in Beckwith Wiedemann syndrome (BWS), whereas maternal duplications have not, to our knowledge, been reported previously in the literature. We present three unrelated patients with maternal duplications of distal 11p. Patient 1 is a 31-year-old female with a de novo inverted duplication of distal 11p, i.e. inv dup del(11)(qter-->p15.5::p15.5-->15.3); this rearrangement was shown to be maternal in origin by microsatellite analysis and methylation-specific polymerase chain reaction. Patient 2 is a 4-year-old female with a derived chromosome 20, which arose from adjacent 1 malsegregation of a maternal t(11;20)(p15.3;q13.33). Patient 3 presented as an intrauterine death with trisomy for the majority of chromosome 11p as a result of 3:1 segregation of a maternal t(11;15)(p11.2;q11.2). In view of the imprinted status of this region, it is pertinent that none of our patients showed features of BWS; indeed, all had growth retardation, in contrast to the overgrowth characteristic of BWS. It is of note that, of the living patients, Patient 1 went into early puberty at 9.5 years and Patient 2 showed breast development in infancy. Both patients shared some dysmorphological features, namely short palpebral fissures, a prominent nasal tip, a short philtrum and 5th finger clinodactyly.